Docking analysis of novel arylidinemalononitrile derivatives as PPAR-γ modulators in the management of type II diabetes mellitus
*Corresponding Author E-mail: firstname.lastname@example.org
Prolonged hyperglycemia often associated with the number of complications such as diabetic neuropathy, retinopathy, nephropathy, cardiomyopathy etc. Diabetic neuropathy is damage to nerves in the body that occurs due to high blood glucose level. In the central nervous system, diabetes exacerbates depression, phobias, anorexia, hypolocomotion, anxiety, cognitive dysfunction etc. The design, docking and analysis of novel arylidine malononitrile-based molecules as derivatives as peroxisome proliferator-activated receptor-γ (PPAR-γ) modulators for antidiabetic activity are reported. Docking studies of designed compounds were carried out using GLIDE (Grid-based ligand docking with emergetics) module version 4.5, Schrodinger, LLC, Newyork, NY, 2007. The software package running on multi-processor Linux PC. GLIDE has previously been validated& applied successfully to predict the binding orientation of many ligands. Docking studies of compounds were performed using human peroxisomes proliferators activated receptor gamma (PDB ID 2PRG) obtained from the RCSB Protein Data Bank. Different arylidine malononitrile derivatives were docked into the ligand binding domain of PPAR-γ by the Glide XP module of Schrodinger, out of those Eight derivatives (AM01, AM02, AM03, AM04, AM05, AM06, AM07, AM08) having Glide XP scores > -9 as compared to the standard drug, rosiglitazone (Glide XP score = -8.34), showed almost similar interaction with the amino acids such as SER-289, GLN-286, and HIE-323 in the molecular docking studies.
PPARγ Agonists, Schrödinger, Diabetes, Arylidene malononitrile, GLIDE, Docking.